PROJECT SUMMARY/ABSTRACT Candidate background: I received my PhD from the University of Montreal (Canada) with a dissertation on pulmonary responses induced by inhaled TiO2 nanoparticles. This research provided me with a solid expertise in lung biology and inhalation toxicology. During my post-doctorate at Louisiana State University (LSU) under the supervision of Dr. Arthur Penn, I received high quality training in tobacco science, including on second-hand smoke and electronic-cigarettes (e-cigs). I am currently an Assistant Professor at LSU, with a research program that focuses on electronic nicotine delivery systems (ENDS) and their pulmonary health effects. Career goals and objectives: My long-term career goals are to become a well-funded independent scientist in the fields of tobacco regulatory science, as well as to attain a tenured Professorship in a research-intensive academic institution. My research goals are to enhance our understanding of the impact of e-cig and JUUL aerosol exposures on lung development and on cardiopulmonary responses. This mentored award will support my career goals by providing protected time to learn new techniques and expertise from my mentoring team. Career development and training activities: I plan to use this mentored award to gain expertise in lung immunology and cardiovascular effects caused by exposures to tobacco-related products to complement my expertise in tobacco-related pulmonary effects. This will be supported by my mentoring team. Dr. Stephania Cormier will be my primary mentor in flow cytometry and lung immunity. Dr. Kent Pinkerton?s mentoring will allow me to expand from solely pulmonary assessment to cardiovascular evaluations of effects induced by ENDS. Dr. Tammy Dugas will be my primary mentor in assessing vascular function in mouse models following exposures to ENDS aerosols. I will also complete a bioinformatics course, attend seminars and present at conferences. Research strategy ? Summary: The prevalence of ENDS use in the US is 8 million adults, of whom 70% are dual-users of classic cigarettes and e-cigs. Little is known regarding the cardiopulmonary effects due to chronic inhalation of ENDS aerosols. Clinical evidence demonstrates declines in lung function and increases in risks of myocardial infarction in healthy dual-users. Since biomarkers of harm with predictive value for cardiopulmonary diseases in dual-users exist, we hypothesize that these biomarkers can serve as a basis for the evaluation of cardiopulmonary toxicity related to long-term inhalation exposures to e-cig or JUUL in single-users. We will study how two ENDS products of different design -- 1) open system e-cig devices, and 2) closed system JUUL devices -- impact individual or combinations of the constituents found in these aerosols, and their toxicity. Our goals are A) to examine the roles that e-liquid constituents play in the chemical profile and in vitro toxicity of ENDS aerosols; and B) to define a panel of biomarkers for cardiopulmonary effects following exposures to either dual- use of cigarettes and e-cigs, or sole exposures to e-cig or JUUL aerosols using in vivo models. Thus, this study has a high societal impact since it will help inform the regulatory agencies and the 8 million adults ENDS users.